This is a multi-center, open-label, randomized, parallel group two-stage phase 1 study with a phase 2 expansion component in pts with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma. Stage 1: Six dose cohorts, 5 using the extended release tablet (ER) formulation (10 mg BID, 20 mg BID, 30 mg BID, 40 mg BID, 50 mg BID) and 1 using the immediate-release (IR) tablet formulation 100 mg QD will be randomized in parallel. After enrollment of 36 patients in Stage 1, a dose of 50 mg BID was determined to be the RP2D. Stage 2: An additional 10 patients with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma (Stage 2a) will be enrolled at the RP2D. Based on the response in Stage 2a, the cohort will be further expanded by up to 19 more patients to a total of 29 patients to confirm the efficacy and safety profile of onapristone in this selected patient population (Stage 2b).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Centre Oscar Lambret
Lille, France
RECRUITINGInstitut Curie Oncologie Medicale
Paris, France
RECRUITINGInstitut Gustave Roussy
Villejuif, France
RECRUITINGStage 1: RP2D of a single agent extended-release tablet formulation of oral onapristone for future clinical development.
Time frame: Baseline to 57 days post-first dose
Stage 2: ORR using RECIST 1.1 in 10-29 patients with recurrent or metastatic uterine endometrioid adenocarcinoma that is APRpos, and to determine the relationship between APR status and onapristone anti-tumor activity.
Time frame: Baseline to 30 Days after last dose
Safety and tolerability of extended-release onapristone tablets BID and of immediate-release onapristone tablets QD
Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and other clinical laboratory values
Time frame: Baseline to 30 Days after last dose
Comparison of safety of extended-release BID vs. immediate release QD schedules
Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and other clinical laboratory values
Time frame: Baseline to 30 Days after last dose
Anti-tumor activity based on tumor assessments (RECIST 1.1) and dates of progression
Time frame: Baseline to 30 Days after last dose
PK of onapristone, mono-demethylated onapristone and other metabolites in plasma and urine
AUC, Cmax, Tmax, t1/2
Time frame: Baseline to 30 Days after last dose
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